甘氨酸对非酒精性脂肪性肝炎肠组织巨噬细胞移动抑制因子表达的影响

Effect of glycine on expression of migration inhibitory factor in intestine of rats with non-alcoholic steatohepatitis

目的:研究探讨甘氨酸对非酒精性脂肪性肝炎大鼠肠组织巨噬细胞移动抑制因子(MIF)表达的影响。方法:将36只雄性SD大鼠,常规饲养1周后,随机分为3组:正常对照组大鼠(采用普通饲料喂养+生理盐水腹腔注射);模型组大鼠(采用高脂饮食+腹腔注射氧四环素);治疗组大鼠(采用高脂饮食+腹腔注射氧四环素+5%甘氨酸),造模4周、8周后分批处死。取肝脏标本做HE染色、观察肝脏形态学变化;检测血浆肿瘤坏死因子-α(TNF-α)、转氨酶(ALT、AST)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和门静脉血浆内毒素(ET)水平;取肠组织做HE染色,并用免疫组化的方法检测肠组织中MIF表达水平。结果:4周、8周时模型组大鼠门静脉ET水平、血浆TNF-α、AST、ALT、IL-6、IL-10均与对照组大鼠比较,差异有显著性意义(P<0.05),治疗组大鼠与同期模型组相比较差异有显著性意义(P<0.05);4周、8周时模型组大鼠肠组织MIF的表达水平较同期对照组大鼠有明显增多(P<0.05),治疗组大鼠肠组织MIF的表达水平与同期模型组相比较,差异有显著性意义(P<0.05)。结论:①采用高脂饮食结合氧四环素腹腔注射制备的大鼠非酒精性脂肪性肝炎(NASH)模型伴有肠源性内毒素血症(IETM)的形成。②在NASH发生发展过程中肠组织MIF表达逐渐增高,可能与肠免疫屏障受损有关;③甘氨酸可拮抗内毒素,下调肠组织MIF的表达水平。

Objective：To explore the effect of glycine on expression of migration inhibitory factor （MIF） in intestine of rats with non-alcoholic steatohepatitis （NASH）.Methods：Thirty-six male SD rats after a week of gaving diet freely were randomly divided into three groups,control group、model group （High-fat diet＋ injected oxytetracycline by intraperitoneal injection） and treatment group （High-fat diet＋ injected oxytetracycline by intraperitoneal injection＋ 5% glycine）.These rats were sacrificed at the 4th,8th weekend during the study,HE staining of liver specimens taken to observe the morphological changes of liver.The blood of abdominal aorta was obstained and the levels of plasma TNF-α、ALT、AST、IL-6、IL-10 and the plasma ET of vena portalis hepatis were measured;take HE staining of intestine.the expression of MIF in intestine tissue were detected with immunohistochemistry.Results：At 4th weekend,8th weekend model group,plasma levels of ET,TNF-α,AST,ALT,IL-6,IL-10 were compared with control group were significantly different （P〈0.05）,treatment group compared with model group was statistically significant difference （P〈0.05）,At 4th weekend,8th weekend of intestinal tissue MIF expression level than the control group had increased obviously （P〈0.05）,treatment group intestinal tissue MIF expression level compared with model group were statistically significant differences （P〈0.05）.Conclusion：①The model of NASH that established by feeding with fat-rich diet and injecting oxytetracycline intraperitoneally accompanies with IETM.②In the process of development of NASH intestinal tissue MIF expression,may increase gradually with impaired immune barrier.③Glycine can down-regulate the level of intestinal tissue MIF by antagonizing with ET.